Parasitic nematodes are a major health concern worldwide, and current strategies for preventing or eliminating nematode infections are insufficient. One possible control strategy is to interfere with the ability of nematodes to locate their hosts. The long-term goal of my research is to better understand how parasitic nematodes locate their hosts, using the free-living nematode C. elegans and the insect-parasitic nematodes Heterorhabditis bacteriophora and Steinernema carpocapsae as models for human-parasitic nematodes. Carbon dioxide is an important host-seeking cue for many parasitic nematodes, yet little is known about the mechanism of CO2 response in nematodes. The overall goal of this proposal is to further our understanding of how parasitic nematodes respond to CO2. I have shown that C. elegans displays acute CO2 avoidance, and I have identified neurons and signaling pathways that are required for this response. I have also found that analogous neurons mediate CO2 attraction in H. bacteriophora. I will now further elucidate the signaling pathways and neural networks that mediate CO2 response in nematodes using molecular, genetic, and neurobiological approaches. I will test the hypothesis that the neural circuits that mediate CO2 response in parasitic nematodes are similar to the neural circuits that mediate CO2 response in free-living nematodes, but contain modifications that reflect the host-seeking requirements of parasites. Parasitic nematodes cause extensive morbidity and mortality worldwide. A better understanding of how parasitic nematodes find and infect their hosts will enable the development of new strategies for preventing nematode infections.